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G Vinci, JP Vernant, M Nakazawa, M Zohair, A Katz, A Henri, H Rochant, J Breton- Gorius and W Vainchenker
INSERM U.91, Service d'Hematologie Hopital Henri Mondor, Creteil, France.
We previously demonstrated that after allogeneic bone marrow
transplantation (BMT) a subset of CD8, HNK1, and DR-positive T lymphocytes
are able to inhibit CFU-GM and BFU-E growth with an HLA-DR restriction. In
this study we investigated whether these cells, present in normal marrow in
low concentration (less than 1%), play the same role. HNK1-positive sorted
marrow cells forming rosettes (E+C) were able to inhibit BFU-E and CFU-GM
growth when added back to the marrow E- C at a ratio of 1:10 (HNK1+
E+C/E-C) in a range from 40% to 60%. This inhibitory effect was also
detected for a cellular ratio of 1:100, which is the normal marrow value
for this subset of T cell. HNK1+ DR+- sorted E+C after
double-immunofluorescent labeling also showed the same inhibitory activity
as the HNK1+ E+C, whereas the negative fraction including all the other E+C
had no detectable inhibitory activity. CD3 and CD8 antigens were also
present on the membrane of these cells, as demonstrated in two cases by
double-immunofluorescent labeling performed with anti-CD3 or anti-CD8
monoclonal antibodies (MoAbs) and HNK1 MoAb, respectively, and subsequent
cell sorting. Blocking experiments, performed by adding in culture anti-CD4
and anti-CD8 MoAbs to HNK1+ T cells showed that only the last MoAb was able
to prevent inhibition of hematopoietic colony growth. These results
confirmed that one subset of CD3+, CD8+, HNK1+, and DR+ T cells was
responsible for in vitro inhibition of normal hematopoiesis. In addition,
this inhibition was genetically restricted to HLA-class II antigens, since
in three co- culture experiments with unrelated bone marrow cells
inhibition occurred only when cells with one haplo-identical HLA-DR antigen
was added back to the culture. Indeed, this effect was really HLA-DR
restricted, since in blocking experiments with different anti-HLA class II
MoAbs (anti-DR, anti-DP, and anti-DQ MoAbs) only an anti-HLA-DR MoAb was
able to prevent the colony growth inhibition by CD3+ HNK1+, or CD8+ HNK1+
E+C. In conclusion, the CD3+, HNK1+, CD8+, DR+ cells may be the T- cell
subset able to inhibit normal hematopoiesis with an HLA-DR restriction.
This article has been cited by other articles:
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